6qir | pdb_00006qir

Crystal structure of CAG repeats with synthetic CMBL3a compound (model I)

spinqualitylabelsall models 6qir, resolution 1.53Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6qir is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.531Å Ligands: J48 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The trinucleotide repeat expansion disorders (TREDs) constitute of a group of >40 hereditary neurodegenerative human diseases associated with abnormal expansion of repeated sequences, such as CAG repeats. The pathogenic factor is a transcribed RNA or protein whose function in the cell is compromised. The disorders are progressive and incurable. Consequently, many ongoing studies are oriented at developing therapies. We have analyzed crystal structures of RNA containing CAG repeats in complex with synthetic cyclic mismatch-binding ligands (CMBLs). The models show well-defined interactions between the molecules in which the CMBLs mimic nucleobases as they form pseudo-canonical base pairs with adenosine residues and engage in extensive stacking interactions with neighboring nucleotides. The binding of ligands is associated with major structural changes of the CAG repeats, which is consistent with results of biochemical studies. The results constitute an early characterization of the first lead compounds in the search for therapy against TREDs. The crystallographic data indicate how the compounds could be further refined in future biomedical studies. Structural insights into synthetic ligands targeting A-A pairs in disease-related CAG RNA repeats.,Mukherjee S, Blaszczyk L, Rypniewski W, Falschlunger C, Micura R, Murata A, Dohno C, Nakatani K, Kiliszek A Nucleic Acids Res. 2019 Sep 30. pii: 5576126. doi: 10.1093/nar/gkz832. PMID:31566242 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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